A mechanism of how alcohol consumption promotes human breast cancer

A mechanism of how alcohol consumption promotes human breast cancer


Alcohol has been shown to increase the risk of breast cancer development. However, the exact mechanism through which ethanol promotes breast cancer is not well characterized. This experiment aims to delve deeper in the specifics of the mechanism, which can be generally described as follows: ethanol is converted to acetaldehyde, a toxic intermediate, which is thought to promote tumor growth. Acetaldehyde induces oxidative stress, which generates reactive oxygen species (ROS) that directly interact with the DNA, contributing to DNA damage. Acetaldehyde is then converted to acetyl-CoA or synthesizes ketone bodies. But the question remains: how does ethanol interact with the tumor’s microenvironment?

Alcohol is known to contribute to the development of fibrotic liver disease and advance the process of fibrosis. Liver fibrosis is caused by liver inflammation: collagen fiber deposits in the extracellular space of liver cells, causing liver cell hardening and loss of blood infusion. During fibrosis, myofibroblasts, which are employed in tissue repair during wound healing but can impair organ function during fibrosis, are generated in the liver, are thought to be related to cancer associated-fibroblasts, and are a key fibrotic component of breast cancer.

In order to study the effects of alcohol on breast cancer, Sanchez-Alvarez et al. performed a series of experiments to examine how ethanol treatment advances the generation of ROS in human fibroblasts, driving tumor growth and metastasis. Their main hypothesis was that ethanol induces metabolic changes in the tumor microenvironment, enhancing epithelial tumor growth.

To test this hypothesis, they used a co-culture system of fibroblasts with MCF7 human breast cancer cells, and human telomerase reverse transcriptase (hTERT)-immortalized fibroblasts, cells that give rise to connective tissue and proliferate indefinitely. They placed fibroblasts in two plates, one with just fibroblasts and another with MCF7 cells, controlling with a plate with untreated cells. Two days later, these cells were treated with ethanol for 72 hours.

They found that ethanol treatment increased ROS production and oxidative stress in cancer-associated fibroblasts. Specifically ROS production increased by 35% in the fibroblasts culture alone when compared with control cells, and 58% in the fibroblasts-cancer cells co-culture. Ethanol was also shown to convert cancer cells to a status associated with more aggressive behavior and a worse prognosis.

Their observations led them to formulate a “two-compartment” metabolic model, in which ethanol treatment induces ketone production in fibroblasts and ketone re-utilization in cancer cells, resulting in tumor cell growth through oxidative mitochondrial metabolism.

Their research is important because it illuminates the mechanism of alcohol consumption metabolically converting “low-risk” breast cancer patients to “high-risk.” This information could be used for breast cancer prevention and therapy, working to reduce the risk of breast cancer in women who consistently drink.

Image source: http://www.cancerresearchuk.org/sites/default/files/alcohol.jpg

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